Microfluidic advances in phenotypic antibiotic susceptibility testing

Campbell, Jennifer; McBeth, Christine; Kalashnikov, Maxim; Boardman, Anna K.; Sharon, André; Sauer-Budge, Alexis F.

doi:10.1007/s10544-016-0121-8

Cited by 31 publications

(17 citation statements)

References 46 publications

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“…Semi-automated susceptibility systems (such as VITEK and MicroScan) decrease the turn-around-time and operator touch-time (culture and colony isolation are still required) compared to traditional culture-based methods, but can add significant cost to the tests [132]. The fastest test still requires 9 h and, therefore, these semi-automated systems do not provide information in time to influence initial treatment decisions [133,134].…”

Section: Microfluidics For Antifungal Susceptibility Testingmentioning

confidence: 99%

“…Since microfluidics promises several advantages over existing macro-scale methods, several microfluidic platforms that can perform rapid antimicrobial susceptibility tests have been developed during the last years (Table 3) [132,135]. The recent development of microfluidic platforms was mostly focused on devices for antibiotics susceptibility testing and much less on antifungals susceptibility testing, although the same designs could, usually, be used for both (e.g., see [136,137]).…”

Section: Microfluidics For Antifungal Susceptibility Testingmentioning

confidence: 99%

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Micro- and Nanoscale Approaches in Antifungal Drug Discovery

Willaert

2018

Fermentation

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Clinical needs for novel antifungal agents have increased due to the increase of people with a compromised immune system, the appearance of resistant fungi, and infections by unusual yeasts. The search for new molecular targets for antifungals has generated considerable research, especially using modern omics methods (genomics, genome-wide collections of mutants, and proteomics) and bioinformatics approaches. Recently, micro-and nanoscale approaches have been introduced in antifungal drug discovery. Microfluidic platforms have been developed, since they have a number of advantages compared to traditional multiwell-plate screening, such as low reagent consumption, the manipulation of a large number of cells simultaneously and independently, and ease of integrating numerous analytical standard operations and large-scale integration. Automated high-throughput antifungal drug screening is achievable by massive parallel processing. Various microfluidic antimicrobial susceptibility testing (AST) methods have been developed, since they can provide the result in a short time-frame, which is necessary for personalized medicine in the clinic. New nanosensors, based on detecting the nanomotions of cells, have been developed to further decrease the time to test antifungal susceptibility to a few minutes. Finally, nanoparticles (especially, silver nanoparticles) that demonstrated antifungal activity are reviewed.Fermentation 2018, 4, 43 2 of 23 antifungal classes have been reported since 2006 [7]. Current antifungal drugs show some limitations: Amphothericin B (a polyene antibiotic) displays a considerable toxicity and undesirable side effects [8,9], issues with pharmacokinetic properties (such as a short half-life of echinocandins) and activity spectrum, a small number of targets [10,11], and they can interact with other drugs, such as chemotherapy agents and immunosuppressants [12,13]. The last approved antifungal (i.e., anidulafungin) by the European Medicines Agency and the Food and Drug Administration (FDA) dates back to 2006 [14]. There is an urgent need for safer and more effective antifungal drugs. Multiple types of antifungal compounds are in clinical development and these new agents have been recently reviewed [15][16][17].Over the last 20 years, several approaches to antifungal discovery have been explored. The traditional approach seeks, first, to identify active compounds from large compound libraries using a panel of fungal pathogens in standardised assays when possible. In the genetic, genomic, or bioinformatics approach, the objective is, initially, to identify broadly represented targets in fungal pathogens and non-pathogens [18]. In this "target-centric" genomic approach, up-front genetic, bioinformatics, and biochemical target prioritisation is performed and, subsequently, an in vitro-based screening of individual targets is achieved. However, an exceedingly high rate of failure has been observed when applying this approach [19]. Additionally, not all bioactive compounds act through a target-specific mechan...

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Section: Microfluidics For Antifungal Susceptibility Testingmentioning

confidence: 99%

Section: Microfluidics For Antifungal Susceptibility Testingmentioning

confidence: 99%

Micro- and Nanoscale Approaches in Antifungal Drug Discovery

Willaert

2018

Fermentation

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“…Microscopy and microfluidics in combination allow for the phenotypic study of individual bacteria or of small bacterial populations in confined volumes 20 . Microfluidic channels handle microliter-sized liquid volumes with microscopic observation routinely possible at the 10-nL scale.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a number of microscopy-based AST platforms have emerged that monitor small bacterial populations 20 . These methods are based on either direct automated counting of bacterial cells 23 , localized density measurement 24 , or observation of metabolite consumption 25 .…”

Section: Introductionmentioning

confidence: 99%

Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates

Kalashnikov

Mueller

McBeth

et al. 2017

Sci Rep

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Bacteremia is a life-threatening condition for which antibiotics must be prescribed within hours of clinical diagnosis. Since the current gold standard for bacteremia diagnosis is based on conventional methods developed in the mid-1800s—growth on agar or in broth—identification and susceptibility profiling for both Gram-positive and Gram-negative bacterial species requires at least 48–72 h. Recent advancements in accelerated phenotypic antibiotic susceptibility testing have centered on the microscopic growth analysis of small bacterial populations. These approaches are still inherently limited by the bacterial growth rate. Our approach is fundamentally different. By applying environmental stress to bacteria in a microfluidic platform, we can correctly assign antibiotic susceptibility profiles of clinically relevant Gram-negative bacteria within two hours of antibiotic introduction rather than 8–24 h. The substantial expansion to include a number of clinical isolates of important Gram-negative species—Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa—reported here underscores the broad utility of our approach, complementing the method’s proven utility for Gram-positive bacteria. We also demonstrate that the platform is compatible with antibiotics that have varying mechanisms of action—meropenem, gentamicin, and ceftazidime—highlighting the versatility of this platform.

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“…Campbell et al . reviewed the most recent advances in microfluidic devices for AST and identification four major strategies: 1) microfluidic incubator platforms; 2) gradient generators; 3) combined assays for identification and AST; and 4) AST based on bacterial death 33 . Several common features emerge from this classification.…”

Section: Introductionmentioning

confidence: 99%

Rapid antibiotic sensitivity testing in microwell arrays

2017

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The widespread bacterial resistance to a broad range of antibiotics necessitates rapid antibiotic susceptibility testing before effective treatment could start in the clinic. Among resistant bacteria, Staphylococcus aureus is one of the most important, and Methicillin-resistant (MRSA) strains are a common cause of life threatening infections. However, standard susceptibility testing for S. aureus is time consuming and thus the start of effective antibiotic treatment is often delayed. To circumvent the limitations of current susceptibility testing systems, we designed an assay that enables measurements of bacterial growth with higher spatial and temporal resolution than standard techniques. The assay consists of arrays of microwells that confine small number of bacteria in small spaces, where their growth is monitored with high precision. These devices enabled us to investigate the effect of different antibiotics on S. aureus growth. We measured the Minimal Inhibitory Concentration (MIC) in less than 3 hours. In addition to being significantly faster than the 48 hours needed for traditional microbiological methods, the assay is also capable of differentiating the specific effects of different antibiotic classes on S. aureus growth. Overall, this assay has the potential to become a rapid, sensitive, and robust tool for use in hospitals and laboratories to assess antibiotic sensitivity.

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Microfluidic advances in phenotypic antibiotic susceptibility testing

Cited by 31 publications

References 46 publications

Micro- and Nanoscale Approaches in Antifungal Drug Discovery

Micro- and Nanoscale Approaches in Antifungal Drug Discovery

Rapid phenotypic stress-based microfluidic antibiotic susceptibility testing of Gram-negative clinical isolates

Rapid antibiotic sensitivity testing in microwell arrays

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